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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1716.)
© 2000 American Heart Association, Inc.

Brief Reviews

Oxidation of LDL by Myeloperoxidase and Reactive Nitrogen Species

Reaction Pathways and Antioxidant Protection

Anitra C. Carr; Mark R. McCall; Balz Frei

From the Linus Pauling Institute, Oregon State University, Corvallis.

Correspondence to Balz Frei, PhD, Linus Pauling Institute, Oregon State University, 571 Weniger Hall, Corvallis, OR 97331-6512. E-mail balz.frei{at}orst.edu

Abstract—Oxidative modification of low density lipoprotein (LDL) appears to play an important role in atherogenesis. Although the precise mechanisms of LDL oxidation in vivo are unknown, several lines of evidence implicate myeloperoxidase and reactive nitrogen species, in addition to ceruloplasmin and 15-lipoxygenase. Myeloperoxidase generates a number of reactive species, including hypochlorous acid, chloramines, tyrosyl radicals, and nitrogen dioxide. These reactive species oxidize the protein, lipid, and antioxidant components of LDL. Modification of apolipoprotein B results in enhanced uptake of LDL by macrophages with subsequent formation of lipid-laden foam cells. Nitric oxide synthases produce nitric oxide and, under certain conditions, superoxide radicals. Numerous other sources of superoxide radicals have been identified in the arterial wall, including NAD(P)H oxidases and xanthine oxidase. Nitric oxide and superoxide readily combine to form peroxynitrite, a reactive nitrogen species capable of modifying LDL. In this review, we examine the reaction pathways involved in LDL oxidation by myeloperoxidase and reactive nitrogen species and the potential protective effects of the antioxidant vitamins C and E.

Key Words: low density lipoproteins • myeloperoxidase • reactive nitrogen species • vitamin C • vitamin E

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